Analysis of insulin signaling pathways through comparative genomics. Mapping mechanisms for insulin resistance in type 2 (non-insulin-dependent) diabetes mellitus.

The precise molecular cause of insulin resistance has not yet been elucidated. Resistance to the normal action of insulin contributes to the pathogenesis of a number of common human disorders, including type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus, hypertension, and the Metabolic Syndrome X, thus constituting a major public health problem. A disease program aimed at combating this disorder should focus on the identification of targets for therapeutic intervention which may overcome insulin resistance and hence the associated metabolic consequences characteristic of the Metabolic Syndrome. Although the primary defect in the pathogenesis of type 2 diabetes is unknown, genetic and environmental factors are likely to contribute to the manifestation of this progressive metabolic disorder, which is usually not clinically apparent until mid-life. Defects at the level of glucose uptake/phosphorylation characterize insulin resistance in skeletal muscle of type 2 diabetic patients. Identification of putative components of the insulin receptor-signaling pathway may offer insights into mechanisms involved in insulin resistance. Enhanced flux of free fatty acids due to impaired lipid metabolism may contribute to impaired insulin secretion and peripheral insulin resistance. Genes regulating lipolysis are prime candidates for susceptibility towards the metabolic syndrome. Here we describe pathways constituting complex interactions that control glucose homeostasis. We will be considering (1) regulation of glucose uptake by the insulin receptor signaling pathway, and (2) control of adipogenesis and insulin sensitivity by the sterol response element binding protein (SREBP) pathway.     

Penicillium piceum infection: diagnosis and successful treatment in chronic granulomatous disease.

Infections due to Penicillium species other than P.marneffei are rare. We identified a boy with X-linked chronic granulomatous disease (X-CGD) with a pulmonary nodule and adjacent rib osteomyelitis caused by Penicillium piceum. The only sign of infection was an elevated sedimentation rate. P. piceum was isolated by fine needle aspirate and from excised infected tissues. Surgical removal and one year of voriconazole treatment were very well tolerated and led to complete recovery. Microbiological, microscopic and molecular studies support the fungal diagnosis. P. piceum should be considered as a relevant pathogen in immunocompromised patients.     

Women's Evaluations of Their Experience in a Multicenter Randomized Controlled Trial of Intrapartum Fetal Pulse Oximetry (The FOREMOST Trial)

Abstract: Background: Fetal pulse oximetry improves the assessment of fetal well‐being during labor. The objective of this study was to evaluate women's satisfaction with their experience with this additional technology. Methods: We surveyed women participating in the FOREMOST trial, a randomized controlled trial comparing the addition of fetal pulse oximetry (FPO) to conventional cardiotocograph (CTG) monitoring (intervention group), versus CTG‐only (control group), in the presence of nonreassuring fetal status during labor. Our survey evaluated 3 aspects of women's experience: labor, fetal monitoring, and participation in the research. The survey was administered within a few days of giving birth and repeated 3 months later. Results: No differences were found between the intervention and control groups for women's evaluations of their labor, fetal monitoring, research, or overall experiences when surveyed on both occasions. Within each study group, a small but statistically significant decline occurred in women's scores for their experience of labor and overall experience from the initial survey close to the time of giving birth, to 3 months later. The magnitude of differences in responses over time was similar for the both groups. Women were more satisfied after a spontaneous or assisted vaginal birth than after cesarean section. Length of time the research midwife was present had a significant positive effect on women's ratings of their experience several days after giving birth (p = 0.006), but no effect at 3 months. Conclusions: The addition of fetal pulse oximetry for the assessment of fetal well‐being during labor did not affect childbearing women's perceptions of fetal monitoring or their labor. Women evaluated their experience in the research process positively overall. Small changes occurred in women's perception of their satisfaction over time. (BIRTH 33:2 June 2006)     

Mode of Delivery and the Survival of Macrosomic Infants in the United States, 1995–1999

ABSTRACT: Background: Although increases in perinatal mortality risk associated with fetal macrosomia are well documented, the optimal route of delivery for fetuses with suspected macrosomia remains controversial. The objective of this investigation was to assess the risk of neonatal death among macrosomic infants delivered vaginally compared with those delivered by cesarean section. Methods: Data were derived from the U.S. 1995–1999 Linked Live Birth‐Infant Death Cohort files and term (37–44 wk), single live births to United States resident mothers selected. A proportional hazards model was used to analyze the risk of neonatal death associated with cesarean delivery among 3 categories of macrosomic infants (infants weighing 4,000–4,499 g; 4,500–4,999 g; and 5,000+ g). Results: After controlling for maternal characteristics and complications, the adjusted hazard ratio for neonatal death associated with cesarean delivery among the 3 categories of macrosomic infants was 1.40, 1.30, and 0.85. Conclusions: Although cesarean delivery may reduce the risk of death for the heaviest infants (5,000+ g), the relative benefit of this intervention for macrosomic infants weighing 4,000–4,999 g remains debatable. Thus, policies in support of prophylactic cesarean delivery for suspected fetal macrosomia may need to be reevaluated. (BIRTH 33:4 December 2006)     

High-resolution optical coherence tomography as a non-destructive monitoring tool for the engineering of skin equivalents

BACKGROUND: Three dimensional skin equivalents are widely used in dermatopharmacological and toxicological studies and as autologous transplants in wound healing. In pharmacology, there is tremendous need for monitoring the response of engineered skin equivalents to external treatment. Transplantation of skin equivalents for wound healing requires careful verification of their quality prior to transplantation. Optical coherence tomography (OCT) is a non-contact, non-destructive imaging technique for living tissues offering the potential to fulfill these needs. This work presents an analysis of OCT for high-resolution monitoring of skin equivalents at different stages during the culture process. METHODS: We developed a high-resolution OCT imaging setup based on a commercially available OCT system. A broadband femtosecond laser light source replaces the original superluminescence diode. Tomograms of living skin equivalents were recorded with an axial resolution of 3 mum and correlated with histology and immunofluorescence images. Comparison with standard low-resolution OCT is presented to emphasize the advantages of high-resolution OCT for this application. RESULTS: OCT is particularly able to distinguish between different layers of skin equivalents including stratum corneum, epidermal and dermal layer as well as the basement membrane zone. The high-resolution OCT scans correlate closely with two key benchmarks, histology and immunofluorescence imaging. CONCLUSIONS: This study clearly demonstrates the benefits of high-resolution OCT for identifying living tissue structure and morphology. Compared with the current gold standard histology, OCT offers non-destructive tissue imaging, enabling high-resolution evaluation of living tissue morphology and structure as it evolves.     

Lung and heart volumes by three-dimensional ultrasound in normal fetuses at 12-32 weeks' gestation.

OBJECTIVE: To establish reference intervals for the fetal right, left and total lung volumes and heart volume between 12 and 32 weeks of gestation. METHODS: Fetal lung and heart volumes were measured using three-dimensional (3D) ultrasound in 650 normal singleton pregnancies at 12-32 weeks. The VOCAL (Virtual Organ Computer-aided AnaLysis) technique was used to obtain a sequence of six sections of each lung and the heart around a fixed axis, each after a 30 degrees rotation from the previous one. The rotation axis for the lungs extended from the apex to the upper limit of the diaphragm dome, and the rotation axis for the heart extended from its apex to its connection to the great vessels. The contour of each of these organs was drawn manually in the six different rotation planes to obtain the 3D volume measurement. In 60 cases the fetal lungs and heart volumes were measured by the same sonographer twice and also by a second sonographer once in order to compare the measurements and calculate intra- and interobserver agreement. RESULTS: The total lung volume and heart volume increased with gestation, from respective mean values of 1.6 and 0.6 mL at 12 weeks to 10.9 and 4.3 mL at 20 weeks and 49.3 and 26.6 mL at 32 weeks. The right to left lung volume ratio did not change significantly with gestation (median, 0.7), whereas the heart to total lung volume ratio increased with gestation from about 0.3 at 12 weeks to 0.5 at 32 weeks. In the Bland-Altman plot, the difference between paired measurements by two sonographers was, in 95% of the cases, less than 0.05, 0.5 and 1.9 mL for each lung at 12-13, 19-22 and 29-32 weeks, respectively, and the corresponding values for the heart volumes were 0.04, 0.4 and 2.3 mL. CONCLUSIONS: In normal fetuses the lung and heart volumes increase between 12 and 32 weeks of gestation. The extent to which in pathological pregnancies possible deviations in these measurements from normal prove to be useful in the prediction of outcome remains to be determined.